Prosthetic devices or prostheses are commonly used in medical procedures to replace or augment defective organs in mammals and humans. Such prostheses are numerous and diverse in structure and application. Examples of prostheses include artificial joints, valve replacements, artificial skin, vascular grafts, shunts, plates and contact and intraocular lenses. Typical prosthetic materials include metals, ceramics, silicone rubbers, polyesters, polyurethanes and/or polysulfones. Synthetic polymers, such as polymethylmethacrylate (PMMA), silicone elastomers and polymers of hydroxyethylmethacrylate (HEMA), are preferred polymers for prosthetic use in general and contact lenses and intraocular lenses in particular.
PMMA has several beneficial characteristics for prosthetic use, including excellent light transmission capability, good optical clarity, resistance to fluid diffusion and in vivo deterioration, ease in processing (injection molding or machining, for example) and ease in implantation.
A problem with typical prior prostheses, such as lens prostheses, is that they are manufactured by machining and also some by injection molding. In the former, the machining process typically leaves circular lathe marks or grooves visible at even relatively low magnification. These machining marks render the lens unusable until the lens surface is smoothed, typically by a mechanical polishing process. However, conventional polishing processes generally take several days to complete, have failure rates in excess of 30% and fail to produce a microscopically smooth surface. The surfaces of injection molded lenses do not show machine lathe marks. However, their surfaces are also not microscopically smooth and reflect the surface finish of the mold.
Also, typical prosthetic devices comprise natural and/or synthetic materials which are highly irregular on the cellular level. These rough prostheses, especially those which are implanted, can cause tissue irritation, cell proliferation, edema and scarring. For example, posterior lens capsule opacification is a prevalent problem among those patients who have received intraocular lens implants comprising conventionally polished PMMA and other similar materials. Pseudophakic precipitates on the surfaces of an intraocular lens can be indicative of microscopic surface irregularities.
It is desirable to modify the surface properties of such abrasive materials without changing the beneficial characteristics thereof by developing a microscopically smooth surface to discourage tissue adhesion and inhibit unwanted cellular growth. Prostheses which do not promote tissue adhesion, which inhibit cellular growth, and which are not otherwise toxic to living systems may be considered "biocompatible." The biocompatible modified surface should be resistant to deterioration over time and should have no adverse effects on contacting tissues and cells.
Those skilled in the art have long recognized the need for biocompatible, surface modified materials for use in prosthetic devices and other materials. For example, U.S. Pat. No. 3,961,379 discloses a bioimplantable device manufactured from a cross-linked, swollen, hydrophilic polymer. These modified polymers must be solid and must be swellable by fluid swelling substances. Once swollen, the solid polymer is polymerized with a modifying substance by, for example, high energy particle radiation.
U.S. Pat. No. 4,189,364 discloses hydrophilic polymers formed in situ by irradiating a mixture of hydroxyalkyl methacrylate and a cross-linking agent. This patent discloses a process for forming hydrophilic polymer articles or hydrophilic polymer coatings on other substrates, such as glass or plastic, by polymerizing a hydrophilic monomer system by high energy particulate irradiation, such as accelerated electrons or nuclear particles including neutrons, protons, alpha, beta and/or gamma particles.
Radiation-induced grafting of acrylic acid onto other polymer films is disclosed by Gazard, M. et al., "Lithographic Technique Using Radiation-Induced Grafting of Acrylic Acid Into Poly(Methyl Methacrylate) Films," Polymer Engineering and Science, 20:16 (1980). Gazard et al. disclose that, under ionizing radiation, polymer properties, such as solubility, may be modified. Ionizing radiation of polymers leads to the formation of free radicals and other intermediates, which may be used to initiate the grafting of a monomer to produce a grafted copolymer with properties different from those of the initial polymer. For example, a grafted copolymer of irradiated PMMA and acrylic acid is insoluble in solvents of PMMA.
U.S. Pat. No. 2,999,056 also discloses that an unsaturated organic acid may be attached to a shaped polymeric structure by ionizing radiation.
Other methods of altering the surface of polymeric objects include exposing the surface of a polymeric article to low temperature plasma or an electrically charged gaseous atmosphere, followed by contacting the surface of the polymeric article with a surface modifying compound as described, for example, in U.S. Pat. No. 4,344,981. This two-step method is generally called plasma-induced coating. Plasma induction has been described generally in U.S. Pat. No. 4,328,257, Yasuda, "Plasma for Modification of Polymers," J. Macromol. Sci. C. Chem., 10(3):383 (1978), Mittal, "Interfacial Chemistry and Adhesion: Recent Developments and Prospects," Pure & Appl. Chem., 52: 1295 (1980) , Akovali, G. and Hasirci, N., "Polymerization of Hexamethyldisiloxane by Plasma on Activated Charcoal: Investigation of Parameters," J. Appl. Polymer Sci., 29:2617 (1984) and Liu, W. T. et al., "Polymethyl Methacrylate Resist Sensitivity Enhancement in X-Ray Lithography by In Situ Polymerization," Appl. Phys. Lett., 44:973 (1984), for example.
Ionized vapor or a plasma discharge is typically created in a vacuum chamber in which the object to be modified is placed. The plasma discharge conditions the surface of the object by creating free radicals and/or ions. It is known, for example, that exposing the surface of an object to a plasma discharge, such as an oxygen plasma, enhances the wettability or hydrophilicity of such a surface. However, such treatment is only temporary. U.S. Pat. Nos. 3,925,178; 3,944,709; 4,072,769; 4,096,315; 4,122,942; 4,123,308; 4,131,691; 4,137,365; 4,214,014 and 4,478,873 disclose examples of polymers whose surface characteristics have been modified by a plasma discharge.
Plasma discharge treatment may also be used to prepare an object for the attachment or grafting of a compound or material to the plasma discharge treated object. For example, a plasma discharge step may be used to condition the surface for grafting by creating free radicals to which a compound or material may be grafted. Such compounds or materials are generally called surface modifiers. Knight, P.M. et al., in "Surface Modification of Intraocular Lenses to Reduce Corneal Endothelial Damage, "Am. Intra-ocular Implants Soc. J., 5:123 (1979) disclose one example of a polymer object having a surface modifier attached thereto using gamma irradiation and radio frequency (RF) gas plasma treatment to generate free radicals on the surface of a PMMA intraocular lens followed by polymerizing hydrophilic monomers, in particular, HEMA and vinyl pyrrolidone, as a coating on the surface of the lens. While the coated surfaces exhibited enhanced hydrophilicity, the coated surfaces were not stable when sterilized by boiling. Surface modification by gamma radiation followed by polymerization on the surface, on the other hand, remained intact through several hours of boiling. However, such coated PMMA surfaces were damaging to rabbit endothelial cells and surfaces coated with dissolvable coatings, such as polyvinyl acetate, were preferred.
Another example of a surface treated polymer is disclosed in U.S. Pat. No. 4,312,575. This patent discloses a soft, highly oxygen permeable, hydrophobic polymeric lens which has a surface coating of an ultra-thin, optically clear, permeable barrier. The coating is the reaction product resulting from a glow discharge polymerization process conducted in a hydrocarbon or halogenated hydrocarbon gaseous atmosphere. While the plasma discharge process, itself, results in a hydrophilic surface, this patent discloses that subsequent exposure to a glow discharge atmosphere of oxygen or ambient oxygen yields a still more hydrophilic surface.
U.S. Pat. No. 4,409,258 discloses a method for rendering contact lenses hydrophilic by bombarding the lens of PMMA or silicone, for example, with a positive ion beam generated by a plasma discharge, such as an oxygen plasma. The lens is thereafter hydrated, preferably at an elevated temperature.
Examples of surface treated polymeric lenses for use in humans are included in U.S. Pat. No. 3,880,818. This patent discloses a soft contact lens that is flexible and physiologically compatible. The lens is made by manufacturing a hard, inflexible prepolymer, such as a hard acrylic acid-type polymer, and reacting the inflexible prepolymer with an alcohol to esterify pendant carboxyl groups with alkyl groups, hydroxy alkyl groups or alkoxyalkyl groups, containing no more than eleven carbon atoms.
U.S. Pat. No. 4,143,949 discloses a discharge polymerization and coating process for making a hydrophilic contact lens from an oxygen permeable, hydrophobic polymer. The hydrophobic lens is placed in a glow discharge apparatus containing an atmosphere comprising a polymerizable organic monomer, such as hydroxyalkyl acrylate or methacrylate, glycidyl methacrylate, propylene oxide or N-vinyl-2-pyrrolidone. The glow discharge is used to polymerize the monomer onto the surface of the contact lens.
Other examples of surface treated polymeric objects include U.S. Pat. Nos. 3,228,741; 3,959,105; 3,985,697; 4,055,378; 4,277,595; 4,405,773; 4,430,458; 4,463,148; and 4,731,080. U.S. Pat. No. 4,731,080, for example, discloses a coated intraocular lens having a hydrophobic cross-linked vinyl-containing silicone polymer placed on the lens surface in solution.
It would be desirable to have a biocompatible, surface modified material and a method for producing the same, wherein the surface of the substrate material is cleaned, and active species, such as ions and free radicals, are produced on the surface by a plasma treatment to enhance subsequent grafting of a polymeric biocompatible material to the substrate surface to provide a substantially permanent, smooth surface on a cellular level. A method for grafting a polymeric biocompatible material to the surface of a substrate is disclosed in our U.S. Patent No. 5,080,924 and U.S. Pat. No. 5,260,093 the disclosures of which are incorporated herein by reference. By pretreating the surface of the substrate material, the smoothness of the substrate and the grafted surface may be improved.